Prognostic Significance of Copy-Number Alterations in Multiple Myeloma
Prognostic Significance of Copy-Number Alterations in Multiple Myeloma
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DOI：
10.1200/jco.2008.20.6136
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发表时间：
2009-09-20
影响因子：
45.3
通讯作者：
Minvielle, Stephane
中科院分区：
文献类型：
--
作者：
Avet-Loiseau, Herve;Li, Cheng;Minvielle, Stephane
目的染色体异常是多发性骨髓瘤的一个特征，但其对全球预后的影响在很大程度上是未知的。患者和方法我们使用高密度单核苷酸多态性(SNP)阵列对192例新诊断的骨髓瘤患者的恶性浆细胞进行了全基因组分析，以确定与预后相关的遗传损害。1q的扩增和1p、12p、14q、16q和22q的缺失是最常见的预后不良的病变，而5、9、11、15和19号染色体的反复扩增则预后良好。多变量分析保留了三个独立的病变：AMP(1q23.3)、AMP(5q31.3)和del(12p13.31)。当调整到已建立的预后变量(即t(4；14)、del(17p)和血清β(2)-微球蛋白[SβM-2])时，del(12p13.31)仍然是最强大的独立不良标志物(P<；.0001；危险比[HR]，3.17)，其次是SβM-2(P<；.0001；HR，2.78)和有利标志物AMP(5q31.3)(P=.0005；HR，0.37)。单纯Amp(5q31.3)和低SβM-2患者预后良好(5年总生存率87%)，而单独Del(12p13.31)或AMP(5q31.3)和Del(12p13.31)和高SβM-2患者预后非常差(5年总生存率20%)。这一预后模型在273例骨髓瘤患者的独立验证队列中得到验证。结论这些发现证明了分子核型分析在预测骨髓瘤预后方面的能力和可及性。此外，驻留在感兴趣的皮损中的基因表达的整合揭示了疾病导致短期生存的假定特征。J Clin Oncol27：4585-4590。(C)2009年美国临床肿瘤学会
PurposeChromosomal aberrations are a hallmark of multiple myeloma but their global prognostic impact is largely unknown.Patients and MethodsWe performed a genome-wide analysis of malignant plasma cells from 192 newly diagnosed patients with myeloma using high-density, single-nucleotide polymorphism (SNP) arrays to identify genetic lesions associated with prognosis.ResultsOur analyses revealed deletions and amplifications in 98% of patients. Amplifications in 1q and deletions in 1p, 12p, 14q, 16q, and 22q were the most frequent lesions associated with adverse prognosis, whereas recurrent amplifications of chromosomes 5, 9, 11, 15, and 19 conferred a favorable prognosis. Multivariate analysis retained three independent lesions: amp(1q23.3), amp(5q31.3), and del(12p13.31). When adjusted to the established prognostic variables (ie, t(4; 14), del(17p), and serum beta(2)-microglobulin [S beta M-2]), del(12p13.31) remained the most powerful independent adverse marker (P < .0001; hazard ratio [HR], 3.17) followed by S beta M-2 (P < .0001; HR, 2.78) and the favorable marker amp(5q31.3) (P = .0005; HR, 0.37). Patients with amp(5q31.3) alone and low S beta M-2 had an excellent prognosis (5-year overall survival, 87%); conversely, patients with del(12p13.31) alone or amp(5q31.3) and del(12p13.31) and high S beta M-2 had a very poor outcome (5-year overall survival, 20%). This prognostic model was validated in an independent validation cohort of 273 patients with myeloma.ConclusionThese findings demonstrate the power and accessibility of molecular karyotyping to predict outcome in myeloma. In addition, integration of expression of genes residing in the lesions of interest revealed putative features of the disease driving short survival. J Clin Oncol 27:4585-4590. (C) 2009 by American Society of Clinical Oncology